CD300d (also known as CD300LD or CMRF35A4) is a member of the CD300 family of transmembrane glycoproteins belonging to the immunoregulatory signaling (IRS) family. CD300d, like most CD300 family members, is found exclusively on myeloid cells, including monocyte and granulocytes . CD300 members contain a V-type immunoglobulin-like domain with an additional pair of cysteine residues in the extracellular domain (ECD), a transmembrane region, and a short cytoplasmic tail . The mature ECD of human CD300d is 146 amino acids (aa) and shares a 48% and 45% identity with mouse and rat CD300d, respectively. CD300d recruits ITAM-bearing Adaptor FceRg. CD300d interacts with all CD300 family members with exception of CD300c, and plays a role in the regulation and/or formation of CD300 complexes on the cell surface and consequently modulate the state of activation of myeloid cells. CD300 family members modulate a broad and diverse array of immune cell processes via their paired activating and inhibitory receptor functions . Mouse CD300d, along with CD300lf, has been identified as a receptor for permissive murine noroviral infection (MNoV) . Further, expression of murine CD300LF on human and other mammalian cell lines confers cross species permissively . Additional research into CD300 family member function during viral infections could help develop novel anti-viral therapies .